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Open Access 26-12-2023 | Hypoxic-Ischemic Brain Injury | Research Article

LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD

Authors: Li Sun, Jun Wan, Bin Sun, Qiuyan Tian, Mei Li, Li-Xiao Xu, Chen-Xi Feng, Xiao Tong, Xing Feng, Xiaofeng Yang, Xin Ding

Published in: Experimental Brain Research | Issue 2/2024

Abstract

The purpose of this study was to identify the target genes of tcon_00044595, elucidate its activation site, and provide novel insights into the pathogenesis and treatment of neonatal hypoxic–ischemic brain damage (HIBD). Through homologous blast analysis, we identified predicted target sequences in the neighboring regions of the long non-coding RNA (lncRNA) tcon_00044595, suggesting that limd1 is its target gene. Starbase was utilized to identify potential candidate microRNAs associated with the lncRNA. The interaction between the candidate microRNAs and limd1 was investigated and validated using various experimental methods including in vitro cell culture, cell transfection, dual fluorescence reporter detection system, and real-time PCR. Homology alignment analysis revealed that the lncRNA tcon_00044595 exhibited a 246 bp homologous sequence at the 3' end of the adjacent limd1 gene, with a conservation rate of 68%. Analysis conducted on Starbase online identified three potential microRNA candidates: miR-3471, miR-883a-5p, and miR-214-3p. Intracellular expression of the limd1 gene was significantly down-regulated upon transfection with miR-3471, while the other two microRNAs did not produce noticeable effects. Luciferase reporter assays identified two interaction sites (UTR-1, UTR-2) between miR-3471 and the limd1 3ʹUTR, with UTR-1 exhibiting a strong influence. Further CCK8 assay indicated a protective role of miR-3471 during low oxygen stroke in HIBD. The potential regulatory relationship between lncRNA (tcon_00044595), miR-3471, and the target gene limd1 suggests their involvement in the occurrence and development of HIBD, providing new insights for investigating the underlying mechanisms and exploring targeted therapeutic approaches for HIBD.

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Title: LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD
Authors: Li Sun
Jun Wan
Bin Sun
Qiuyan Tian
Mei Li
Li-Xiao Xu
Chen-Xi Feng
Xiao Tong
Xing Feng
Xiaofeng Yang
Xin Ding
Publication date: 26-12-2023
Publisher: Springer Berlin Heidelberg
Keyword: Hypoxic-Ischemic Brain Injury
Published in: Experimental Brain Research / Issue 2/2024
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-023-06755-x

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